There have been some great presentations outlining both developments in genomic technology (read: next-generation sequencing) and applications of those technologies to biomedical research. A major highlight for me has been a number of presentations on exome sequencing (capturing and sequencing all of the protein-coding regions of the genome), especially Debbie Nickerson‘s impressive outline of her group’s work using this technology to hunt down mutations underlying rare, severe Mendelian diseases, and her plans to apply the technology to over 7,000 samples over the next year to explore the genetic origins of more complex traits.

Exome sequencing is the technology of the moment because it provides access to the best-characterised functional regions of the genome at a substantially lower cost than whole-genome sequencing. However, it is not without its drawbacks: capture methods are still far from perfect, resulting in uneven coverage across the genome and resulting difficulties for downstream analysis, and of course the approach will miss any variants found outside coding regions.

Several speakers discussed cost-benefit analyses comparing exome sequencing with whole-genome sequencing; it’s clear that this is a technology with a very limited lifespan (perhaps as little as twelve months) before sequencing costs drop to the point that whole-genome analysis is more cost-effective.

As always, much of the most interesting material at this meeting has been found outside the sessions, in the buzz and hype surrounding the increasingly crowded field of next-generation sequencing.

Much of that buzz surrounds the ongoing scuffle between the two dominant second-gen sequencing providers, Illumina and Life Technologies. Illumina, currently secure in first place in the sequencing race, presented some impressive statistics and early data from its new instrument (the HiSeq 2000), which Luke Jostins has already discussed in detail. Life Tech is responding on a number of fronts, including its new SOLiD 4 technology and the formal announcement of its in-development third-generation instrument (code-named Project Starlight). I’ll have some more detail on this over the next couple of days.

One of the most eagerly awaited setpieces of the conference was the unveiling of the third-generation sequencing instrument developed by Pacific Biosciences. Kevin Davies from Bio-IT World has a superb piece describing his attendance at a rather exclusive event previewing the instrument. In addition to describing the (surprisingly bulky) instrument, Davies draws out some observations from PacBio CEO Hugh Martin on the company’s competitors:

Martin argues that 2nd-generation technology is flattening out, despite the healthy competition between Life Technologies and Illumina. “454 Life Sciences is not moving very much relative to longer read applications. Helicos, I think, has become sort of irrelevant. Complete [Genomics]–it’ll be interesting to see what happens to their cost model, because I think a lot of people in the world are going to be enabled to be service providers using [Life and Illumina] boxes to compete with Complete.”

PacBio also announced its first ten early-access customers (notably, none outside the US North America), and also got an extended plug in a presentation by Washington University’s Elaine Mardis on cancer genomics (preceded by a disclaimer noting that Mardis is a member of PacBio’s advisory board). Overall, I can’t help but be underwhelmed by everything I’ve seen from PacBio so far, especially compared to the dramatically over-hyped claims (15 minute genome, anyone?) the company has become notorious for over the last couple of years.

There’s also been a debut by a small company, Ion Torrent; I’m still digesting the company’s material and will have more on them later.

Finally, Complete Genomics continues to impress. The company’s single-minded focus on creating an extraordinarily efficient factory producing a single high-value product – complete human genomes – seemed like a risky move when it launched a year ago, but now looks extremely shrewd. I’ll have more about Complete after the presentation from their CSO Rade Drmanac on Saturday, where we’ll apparently hear some early results regarding several technical advances the company has made over the last few months.